The technique known as Coulter counting was first proposed by Wallace H. Coulter in the late 1940s as a technique for the high speed counting of red blood cells. Also referred to as resistive pulse sensing, Coulter counting may be used to measure physical parameters of analytes in electrolyte solution including size (volume), charge, electrophoretic mobility and concentration. In this technique, two reservoirs of solution are separated by a fluidic constriction of known dimensions. The application of a constant DC voltage between the two reservoirs results in a baseline ionic current that is measured. The magnitude of the baseline current is related to the conductivity of the electrolyte, the applied potential, the length of the channel, and the cross-sectional area of the channel. If an analyte is introduced into a reservoir, it may pass through the fluidic channel and reduce the observed current due to a difference in conductivity between the electrolyte solution and analyte. The magnitude of the reduction in current depends on the volume of electrolyte displaced by the analyte while it is in the fluidic channel.
A benefit of the resistive pulse sensing technique is that it may be scaled down to enable the detection of nanoscale analytes through the use of nanoscale fluidic constrictions. This capability led to the development of solid-state nanopores for detecting nanoscale molecules such as DNA.
In the case of DNA translocation through a nanopore, the physical translocation is driven by the electrophoretic force generated by the applied DC voltage. This driving force and the detected signal are, therefore, typically inseparably coupled. The decoupling of these two effects may be desirable because the optimal potential for physical translocation is different from that of optimal measurement.
Transverse electrodes have been proposed to provide a transverse electric field and electric current to sense biomolecules confined in a nanofluidic channel. See Liang and Chou 2008 Liang, X; Chou, S. Y., Nanogap Detector Inside Nanofluidic Channel for Fast Real-Time Label-Free DNA Analysis. Nano Lett. 2008, 8, 1472-1476, which is incorporated herein by reference in its entirety. The analytes are moved through the channel with an electrophoretic force generated by current-carrying electrodes at the ends of the nanochannel, therefore decoupling the measurement from the translocation speed.